Contribution of endogenous endothelin in the enhanced coronary constriction in DOCA-salt hypertensive rats
Bibliographic record
Abstract
OBJECTIVE: The present study was performed to evaluate the hypersensitivity to vasoconstrictors in coronaries from uninephrectomized hypertensive rats (HTR), after a 2-week deoxycorticosterone acetate (DOCA)-salt treatment, in comparison with uninephrectomized age-matched normotensive rats (NTR). DESIGN AND METHODS: Coronary resistance was recorded from isolated Langendorff hearts perfused at a constant flow rate. RESULTS: Cumulative dose-response curves to vasopressin, angiotensin II and endothelin in HTR showed an enhanced maximal response, in comparison with NTR (P< 0.05). In contrast, the sensitivity to U-46619, a thromboxane-mimetic agonist, was reduced in HTR in comparison with NTR (P< 0.05). In the presence of ET(A)/ET(B)-receptor antagonists, LU-302 872 (10 micromol/l) and PD-142 893 (0.1-1 micromol/l), cumulative dose-response curves to vasopressin and angiotensin II showed a reduced maximal response in HTR compared with NTR (P< 0.05). LU-302 872 did not change the responsiveness to U-46619 in both groups. Perfusion of hearts from NTR with a subpressor concentration of endothelin-1 (10 pmol/l) potentiated the responsiveness to vasopressin and angiotensin II, but not that of U-46619 (P< 0.05). Hypertension did not alter the dose-response curves obtained with phorbol 12-myristate 13-acetate, an activator of protein kinase C, Bay K 8644, a L-type calcium-channel activator, and KCl. Measurement of endothelin release by radioimmunoassay in the coronary effluent, before and during dose-response curves to vasopressin, angiotensin II and U-46619, showed no significant increase by the vasoconstrictors, although basal endogenous endothelin was increased in HTR (P< 0.05). CONCLUSION: Two-week DOCA-salt hypertension is associated with enhanced coronary vasoconstrictor effects of endothelin, vasopressin and angiotensin II. An increased basal release of endogenous endothelin in coronaries from HTR, along with an enhanced responsiveness of the coronary smooth muscle to endothelin, may contribute to the potentiated response to vasoconstrictors. L-type calcium-channels and protein kinase C are not involved in this increased coronary reactivity to vasoconstrictors in HTR.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".